Preeclampsia is the leading cause of maternal and fetal morbidity and mortality in the world. This pregnancy- specific syndrome generally develops after the twentieth week of gestation, and can lead to major maternal morbidity or death. At the same time, reduced placental blood flow can lead to fetal growth restriction, premature delivery for maternal or fetal indications, and fetal morbidity and mortality. At the present time there are no proven interventions to prevent preeclampsia. The overall goal of this research will be to identify women in the first trimester who are at increased risk of developing preeclampsia later in pregnancy. The specific aims of this project are: (1) To compare first trimester levels of inhibin A, PP13, activin A and ADAM12 from women who subsequently developed preeclampsia to levels seen in control women, and (2) To develop a multivariate prediction model for preeclampsia using these first trimester maternal serum markers in combination with a panel of maternal characteristics as recorded in our database. The nested case control study will select preeclamptic and control (women who did not develop preeclampsia) patients from existing data contained in the University of Colorado Department of OB-GYN Database and a database from the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Maryland. By merging data from these two centers we will have access to comprehensive clinical data including maternal characteristics and outcomes from 4,000 pregnancies (approximately 2,000 women from each site as of December, 2008). Blood samples drawn from these patients between 9 and 14 weeks gestation have been stored in sample repositories at both institutions, and will be available for assay. The study will make use of a well established research team, preexisting and well-characterized data, access to PP13 and ADAM12 assays, and collaboration with accomplished experts in devising prediction modeling in adverse perinatal outcome. The aims of the proposed study have been identified as a 2008 NIH Research Priority for Women's Health in a document issued by the Research Subcommittee of the NIH Coordinating Committee on Research on Women's Health in November, 2007. This document specifically encouraged research "in early detection and treatment, including the development of novel tools to identify and validate biomarkers in relation to disease risk". The study is significant because preeclampsia is a leading cause of fetal and maternal death worldwide, and first trimester prediction of preeclampsia will have the effect of promoting and accelerating the search for prophylactic and therapeutic agents for preeclampsia. In addition identification of early markers of preeclampsia would lead to closer scrutiny of at risk pregnancies and may provide information regarding the mechanism of the disease. PUBLIC HEALTH RELEVANCE: A critical goal in improving the care of women with preeclampsia is to identify women at risk even before the disease is manifest. The ability to identify these women early in their pregnancy would allow closer monitoring in the short term, and in the longer term could lead to future trials of promising drugs or techniques that might forestall or even prevent the disease. Accomplishing either of these objectives would lead to reduced morbidity and mortality of both mothers and babies.